@article{f555a458ead1413c962d2e84d8c2c74f,
title = "Synthesis and biological evaluation of C-4 substituted phenoxazine-bearing hydroxamic acids with potent class II histone deacetylase inhibitory activities",
abstract = "Class II histone deacetylases (HDACs) are considered as potential targets to treat Alzheimer{\textquoteright}s disease (AD). Previously, C-3 substituted phenothiazine-containing compounds with class II HDAC-inhibiting activities was found to promote neurite outgrowth. This study replaced phenothiazine moiety with phenoxazine that contains many C-3 and C-4 substituents. Some resulting compounds bearing the C-4 substituent on a phenoxazine ring displayed potent class II HDAC inhibitory activities. Structure-activity relationship (SAR) of these compounds that inhibited HDAC isoenzymes was disclosed. Molecular modelling analysis demonstrates that the potent activities of C-4 substituted compounds probably arise from π-π stacked interactions between these compounds and class IIa HDAC enzymes. One of these, compound 7d exhibited the most potent class II HDAC inhibition (IC50= 3–870 nM). Notably, it protected neuron cells from H2O2-induced neuron damage at sub-μM concentrations, but with no significant cytotoxicity. These findings show that compound 7d is a lead compound for further development of anti-neurodegenerative agents.",
keywords = "Histone deacetylase (HDAC), neuron cells, phenoxazine, structure-activity relationship (SAR)",
author = "Chu, \{Jung Chun\} and Tseng, \{Hui Ju\} and Lee, \{Sung Bau\} and Hsu, \{Kai Cheng\} and Hsin, \{Ling Wei\} and Liang, \{Ru Hao\} and Lin, \{Tony Eight\} and Gao, \{Nain Chu\} and Chen, \{Liang Chieh\} and Lu, \{Wan Hsun\} and Wang, \{Andrew H.J.\} and Huang, \{Wei Jan\}",
note = "Funding Information: This work was supported by the Ministry of Science and Technology, Taiwan. We gratefully acknowledge the support from the National Science and Technology Council (MOST111-2320-B-038–042-MY3 and MOST110-2320-B-038–024-MY3) in Taiwan. Funding Information: We gratefully acknowledge the support from the National Science and Technology Council (MOST111-2320-B-038–042-MY3 and MOST110-2320-B-038–024-MY3) in Taiwan. Publisher Copyright: {\textcopyright} 2023 The Author(s). Published by Informa UK Limited, trading as Taylor \& Francis Group.",
year = "2023",
doi = "10.1080/14756366.2023.2212326",
language = "English",
volume = "38",
journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",
issn = "1475-6366",
publisher = "Taylor and Francis Ltd.",
number = "1",
}